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Molecular and Cellular Biology, August 1999, p. 5247-5256, Vol. 19, No. 8
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Mutations in Translation Initiation Factors Lead to Increased Rates of Deadenylation and Decapping of mRNAs in Saccharomyces cerevisiae

David C. Schwartz1 and Roy Parker1,2,*

Department of Molecular and Cellular Biology1 and Howard Hughes Medical Institute,2 University of Arizona, Tucson, Arizona 85721

Received 25 January 1999/Returned for modification 11 March 1999/Accepted 23 April 1999

The turnover of most mRNAs in Saccharomyces cerevisiae begins with deadenylation followed by decapping and 5'right-arrow3' exonucleolytic digestion. An important question involves the mechanisms that allow particular mRNAs to exhibit different rates of both deadenylation and decapping. Since the cap structure plays a critical role in the assembly of translation initiation factors, we hypothesized that the status of the cytoplasmic cap binding complex would affect the rate of decapping. To test this hypothesis, we examined mRNA decay rates in yeast strains that were defective in several translation initiation factors that are part of the cap binding complex. These experiments yielded three significant observations. First, any mutation known to inhibit translation initiation also increased the rate of decapping. Second, decapping still occurred only after deadenylation, suggesting that the ability of the poly(A) tail to inhibit decapping does not require efficient translation of the transcript. Third, mutants with defects in translation initiation factors also showed an increase in the rate of deadenylation, suggesting that the rate of deadenylation may be controlled primarily by the translation status of the transcript. These results argue that the nature of the translation initiation complex is a critical factor in determining the mRNA half-life. This view also implies that some cis-acting sequences that modulate mRNA decay rate do so by affecting the translation status of the transcript.


* Corresponding author. Mailing address: Howard Hughes Medical Institute, University of Arizona, Tucson, AZ 85721. Phone: (520) 621-9347. Fax: (520) 621-4524. E-mail: rrparker{at}u.arizona.edu.


Molecular and Cellular Biology, August 1999, p. 5247-5256, Vol. 19, No. 8
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



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